The Animal Core serves as a centralized resource that provides mice with genetic deletions or mutations to the members of the Center, other research groups at the university, and the general scientific community. The animal lines that we have focused on thus far have deletions of genes in three systems: opioid receptors (mu-, delta- and kappa-receptor subtypes), cannabinoid receptors (CB1, CB2 and CB1/2 double knockouts), and chemokine receptors and ligands (CCL2, CCR2 and CCR5). Significant progress to date has been made by multiple laboratories associated with the Center using these lines. In addition to continuing to breed the existing animal lines, in the next grant period we will breed combinatorial mutant mice with genetic deletions of multiple genes such as two opioid receptors (Le. mu/delta) or an opioid receptor together with a chemokine (Le. mu/CXCR2). In addition, we will include two new models: mice with conditional gene deletions using the Cre-LoxP system and mice that express specific proteins tagged with enhanced Green Fluorescent Protein (EGFP). Conditional gene deletions allow investigators to evaluate the function of specific proteins of interest within a specific cell type or brain region or within a specific time window without the embryonic lethality and/or developmental compensatory responses that limit the utility of constitutive knockout strategies. The first of these mice that the Animal Core will breed will be a CXCR4-floxed mouse line. EGFP-tagged mice allow researchers to monitor the expression and localization of the tagged protein of interest in vivo or in vitro without impacting protein function and without reliance on antibodies. The first two strains of EGFP transgenic mice that we propose to breed are the CXCR4- and CX3CR1-EGFP lines. Multiple proposals for the use of the existing and new animal lines are detailed in the application. In-house breeding and use of the same animal strains by multiple investigators enhances collaborative studies and increases scientific synergy. Furthermore, because some of our existing and proposed mouse strains are unavailable commercially, the Animal Core can serve as a national resource, providing unique mouse models to the scientific community.